Jiang Lan, Gao Ze-Ming, Ye Lin, Zhang Ai-Ying, Feng Zeng-Guo
School of Materials Science and Engineering, Beijing Institute of Technology, Beijing 100081, China.
Biomater Sci. 2013 Dec 29;1(12):1282-1291. doi: 10.1039/c3bm60112a. Epub 2013 Aug 19.
A pH-sensitive nano antitumor drug delivery system was prepared by conjugating doxorubicin (DOX) to amphiphilic polyrotaxane (PR)-based block copolymers through a pH-sensitive cis-aconityl moiety. The resulting polymer-drug conjugates were able to self-assemble into polymeric micelles in an aqueous solution with diameters varying from 297 nm to 178 nm after the conjugation as evidenced by DLS measurements. The pH-sensitive cis-aconityl linkage provided a controlled and sustained release of DOX over a period of more than 5 days in an acidic environment mimicking the tumor microenvironment, and a negligible amount of release in an environment with physiological pH. The nanoparticles had lower cytotoxicity than the free drug and can efficiently transfer and release the drug into HeLa cells. With these promising properties, the PR-based block copolymers have the potential to be carriers for the controlled release of antitumor drugs.
通过基于两亲性聚轮烷（PR）的嵌段共聚物，利用pH敏感的顺乌头酰部分将阿霉素（DOX）偶联，制备了一种pH敏感的纳米抗肿瘤药物递送系统。动态光散射测量结果表明，所得聚合物-药物偶联物能够在水溶液中自组装成聚合物胶束，偶联后直径从297nm变化到178nm。pH敏感的顺乌头酰连接在模拟肿瘤微环境的酸性环境中，能在超过5天的时间内实现阿霉素的可控和持续释放，而在生理pH环境中的释放量可忽略不计。纳米颗粒的细胞毒性低于游离药物，并且能够有效地将药物转运并释放到HeLa细胞中。基于这些有前景的特性，基于PR的嵌段共聚物有潜力成为抗肿瘤药物控释的载体。
